![]() Importantly, AMP injection may also reduce ischemic brain injury in experimental mouse models ( 6). Recent studies have shown that injection of AMP in mice can cause a rapid drop in core body temperature, resulting in a hypometabolic state similar to that seen with therapeutic hypothermia and in animals undergoing hibernation ( 4, 5). However, the equipment needed to induce hypothermia is complex and the rate of cooling is slow, which limits the utility of this method in critical care settings ( 3). ![]() One attractive approach is therapeutic hypothermia that slows metabolism and thereby reduces nerve damage ( 2). Current treatment strategies to reduce brain damage in these patients are limited. Permanent brain damage is a frequent consequence of these and similar conditions that deprive the brain of oxygen. ![]() Ischemia and reperfusion injury are unresolved problems that cause major clinical complications, for example in cardiac arrest, stroke, and trauma patients ( 1). Further examination of these mechanisms may lead to new treatments that preserve organ function in critical care patients. These findings suggest that AMP induces a hypometabolic state that slows mitochondrial respiration, reduces oxygen demand, and delays the processes that damage mitochondria in the brain and other organs following hypoxia and reperfusion. Pretreatment with an intraperitoneal injection of AMP almost doubled the survival time of mice under hypoxic (6% O 2) or anoxic (<1% O 2) conditions when compared to untreated mice. AMP treatment increased intracellular AMP levels and activated AMP-activated protein kinase (AMPK), which resulted in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and of mitochondrial and cytosolic Ca 2+ signaling in resting and stimulated neurons. Adding AMP to mouse or human neuronal cell cultures dose-dependently reduced the membrane potential (ΔΨm) and Ca 2+ signaling of mitochondria in these cells. We studied the underlying mechanisms and found that AMP transiently reduces the heart rate, respiratory rate, body temperature, and the consciousness of adult male and female C57BL/6J mice. It has been previously reported that injection of naturally occurring adenosine 5’-monophosphate (AMP) can rapidly induce hypothermia in mice. Therapeutic hypothermia can reduce ischemia-induced brain damage, but cooling procedures are slow and technically difficult to perform in critical care settings. The brain is particularly vulnerable because hypoxia rapidly damages neurons due to their heavy reliance on oxidative phosphorylation. Ischemia and reperfusion injury following severe trauma or cardiac arrest are major causes of organ damage in intensive care patients.
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